Moreover, two recent observational cohort studies by Chavarro and colleagues evaluated the association between soy consumption and in vitro fertilisation outcomes(Reference Vanegas, Afeiche and Gaskins40,Reference Chavarro, Mnguez-Alarcn and Chiu42) . Isoflavones are plant-based compounds found almost exclusively in beans, like soybeans, that mimic the action of the hormone estrogen. Li, Hang Furthermore, phytoestrogens appear to act on SHBG synthesis by altering mRNA levels in hepatocarinoma human cells treated with genistein 20M(Reference Mousavi and Adlercreutz85), and modulating the balance between bound and free steroids or competing with endogenous sex hormones for the active site binding of the carrier(Reference Dchaud, Ravard and Claustrat86). Regarding isoflavones, the equol metabolite derives from the precursor daidzein by the action of intestinal bacteria. In addition, equol acts on incretins levels in endocrine L cell line GLUTag cells at concentration ranging from 50 to 300M, with long-term metabolic consequences(Reference Harada, Sada and Sakaguchi79). (Reference Moher, Liberati and Tetzlaff24). Journal of Clinical Endocrinology and Metabolism randomized 70 women with PCOS into two groups to take either 50 mg/d soy isoflavones or a placebo for 12 weeks. One of the first research papers to look directly at soy and fertility outcomes was from the Adventist Health Study-2. Additional considerations regarding hormonal influences will be discussed in the next paragraph. Regarding the observational studies available, in 2015 Venegas et al. A slight increase of approximately 1d (MD: 105, 95% CI 013, 197) was seen compared with the control, with no significant effects in the length of luteal and follicular phases. However, stratification for the control group or PCOS patients did not show a significant correlation between androgens and equol production. These changes may have resulted in the mild, non-clinically relevant prolongation of menstrual cycle, as discussed in the previous section. The authors responsibilities were as follows: G. R. study conception and drafting the manuscript. While the observational data better reflect the effects of diet in free-living conditions compared with experimental settings of clinical trials, the use of food frequency questionnaires exposes to possible misclassification and measurement errors. In another prospective study, 471 healthy American women were followed for 12 months or until delivery without showing significant correlations between urinary isoflavones, quantified by HPLC-MS analysis, and fertility, defined with adjusted Cox Model using time-to-pregnancy assessment(Reference Mumford, Sundaram and Schisterman39), while lignan concentrations in urine were significantly associated with shorter time to pregnancy. Ma, Haoyue The study involved a large number of couples seeking pregnancy. Soy Isoflavones supplements and Fertility Infertility is a condition that prevents pregnancy despite having regular sexual intercourse with your partner for at least a year. Many of its components show an antioxidant activity that can at least partially explain its effectiveness(Reference Rizzo9). conducted another prospective cohort study on 239 American women undergoing assisted reproductive technology(Reference Chavarro, Mnguez-Alarcn and Chiu42). Isoflavones also bind to ER receptor, albeit with lower affinity. The use of surveys only through self-administered questionnaires, although validated, is easily exposed to self-reporting errors or incompleteness and misclassifications derived from the database used for food intake quantification. Eating Places. Green, Eulalee Soy protein has gained considerable attention for its potential role in improving risk factors for cardiovascular disease (CVD). between 128 women fed with soy-based formula and 268 women fed with cow milk formula during infancy. Manuscripts exploring multiple aspects were discussed in different paragraphs, where deemed necessary. The interaction between isoflavones and ER estrogen receptor results in a competitive effect which in turn blunts endogenous estrogens action(Reference Rosselli, Reinhart and Imthurn72), as suggested by estrogenic activity of biochanin A and genistein on BT-474 human breast cancer(Reference Zand, Jenkins and Diamandis73). In a logical perspective, the effect of soy cannot be attributed to the effect of its isoflavones alone. Based on our literature search, we also identified two observational studies: a cross-sectional study published in 1997 by Nagata et al. PMCID: PMC8922143. This could be due to the scarcity of studies on the topic and the presence of few clinical trials, adequately designed to evaluate soy effect on fertility with consistent timing, with an adequate number of participants, blinding, and randomisation for physiological conditions and the presence of equol-producer individuals. (Reference Wu, Stanczyk and Hendrich28). Microbial alpha diversity and glucose homeostasis improved in PCOS group after isoflavone intervention, resembling the control group profile at baseline. Han, Jing However, the number of participants was limited for a cross-sectional study, and dietary survey through frequency questionnaires in the absence of an assessment of blood or urine isoflavone levels could lead to uncertainty. Pending further confirmation, soy and its components do not appear to have a clinically relevant influence on menstrual cycle in healthy women. Moreover, isoflavones act as selective estrogen receptor modulators (SERMs) showing both agonist and antagonist effects on ER, with subsequent estrogenic, anti-estrogenic or even neutral effects(Reference Liu, Li and Chen14). Overall, soy and soy components consumption do not seem to perturb healthy women's fertility and can have a favourable effect among subjects seeking pregnancy. Most women taking soy isoflavones to induce ovulation take around 150-200 mg a day on cycle day 3 -7 or 5-9. was a pilot study without a characterisation of diet among participants and without data on soy composition (isoflavone or antioxidant contents). It affects one out of every six couples and affects the majority women aged between 15 to 44 years. In the previously mentioned meta-analysis by Hooper and colleagues(Reference Hooper, Ryder and Kurzer59), reduction of about 22% of FSH (SMD: 045UI/l, 95% CI 079, 011, P=001) and of about 4% of LH (SMD: 034IU/l, 95% CI 068, 001, P=005) were related to the intake of soy or isoflavones. Products; Resources; My Account; Talk to a D&B Advisor 1-800-280-0780. Business Directory. Regarding the two mentioned studies, the use of very high amounts of isoflavones is noteworthy because it is not possible to obtain such a dose through diet, therefore the effects found can be interpreted as a pharmacological and not nutritional intervention. The urinary or serum levels of isoflavones did not affected progesterone levels in the multiple regression analysis. Jacobsen and colleagues included 11688 American women aged 3050 years of age who participated in Adventist Health Study-2 (AHS-2)(Reference Jacobsen, Jaceldo-Siegl and Knutsen38). Get company information for Twins Club, Inc. in RANCHO CUCAMONGA, CA. Longer, not clinically relevant duration of menstrual bleeding (adjusted MD: 037d, 95% CI 006, 068), without differences in severity of menstrual flow was observed. The deleterious effects of these compounds, as metabolites of clover isoflavones, were first documented in 1946 by Bennetts and co-workers studying New Zealand ewes expressing clover disease, an infertility syndrome ( Bennetts, Underwood, & Shier, 1946 ). Soy is a key food in human nutrition. However, for articles selection, we used search engines both for scientific literature and specific for clinical trials, without filters application that could have limited the results. This could have introduced other confounding factors such as the influence of male on couple's fertility or possible changes in habits caused by the desire to conceive. In another clinical trial already discussed, although no changes in cycle length were found following soy foods intervention in twenty women with a follow-up of at least seven menstrual cycles, a significant reduction in follicular phase by 93% (P<005) in estradiol concentrations was observed, but not in luteal phase(Reference Wu, Stanczyk and Hendrich28). However, the intake of isoflavones in diet has not been investigated, and therefore, it was not possible to define the presence of equol-producers among participants. Soy is a very popular food and its consumption is part of the traditional cuisine of South-East Asian countries. Shop Soy Isoflavones Menopause Relief and read reviews at Walgreens. The individual conversion capacity, equol-competence, offers a useful tool for estimating the biological effect of these compounds(Reference Zubik and Meydani15). The limitations of these studies have already been discussed in the previous paragraph. Despite the 6-month duration of the clinical trial, the lack of a placebo group, the absence of characterisation of equol-competence among individuals and the limited number of participants reduced the strength of the results obtained. In the first study, the authors administered soy milk to six American women aged 2229 for 1 month, comparing outcomes with baseline(Reference Lu, Anderson and Grady26). However, even in the West, it is currently widely used, especially due to its versatility in plant-based products for health purposes and vegetarian diets(Reference Rizzo and Baroni1). Following the removal of eighty-four duplicates, the selection was made through titles, abstracts and full-text reading. Only three articles declared power analysis to assess adequate sample size(Reference Strom, Schinnar and Ziegler30,Reference Jamilian and Asemi43,Reference Haudum, Lindheim and Ascani46) . Deepak Kumar, Komal It is widely used in eastern traditional cuisine and it has recently diffused among self-conscious and vegetarian diets. Furthermore, hormone levels were evaluated only at baseline, without taking into account the differences between the two groups. These substances could play a role in the ovaries circulatory functions(Reference Oyawoye, Abdel Gadir and Garner50). Patients showed plasma androgens levels above or at the upper limit the normal range, at baseline. Main characteristics of selected studies. The fertility concept differs from the fecundity one, which refers to reproductive potential and depends on reproductive physiology, from the production of gametes phase to the ability to carry a pregnancy to term. However, the terms are often interchangeably, being closely associated with the possibility of giving birth to children. Even if the exact conversion mechanism has not been characterised yet, a limited conversion capacity in Western populations (about 25%) has been highlighted, as opposed to the greater competence of Asian populations (50%), estimated through urinary equol excretion(Reference Setchell, Brown and Lydeking-Olsen17). Concerns that the phytoestrogens (isoflavones) in soy may feminize men continue to be raised. However, among fertile individuals, it may have a neutral effect, as discussed in the previous paragraphs. Get the latest business insights from Dun & Bradstreet. Soya Isoflavones are derived from soya beans. In 2000, Wu et al. However, urinary phytoestrogen levels were only detected at baseline and this increased the correlation uncertainty. Keywords were searched in titles and abstracts and combined with MeSH terms, where available, adapting the query format based on the search engine used. CA. There was no relationship between isoflavone intake and reported problems becoming pregnant. These conclusions cover several physiological aspects, including those concerning women's fertility, consistently with the conclusions of this review that highlighted nine additional articles compared with Messina's selection about the topic. For these reasons, studies that evaluated the ovarian hormones secretion were aimed at exploring the potential beneficial effect of soy on breast cancer prevention, but they were not designed for the evaluation of endocrine consequences, including fertility. 2 highlights the main cellular mechanisms attributed to isoflavones. Adapted from Moher et al. No significant differences were found in the spontaneous abortion rate, the number and quality of embryos transferred or oocytes fertilised. This was a short pilot study with a small sample size in subgroups. In the first of the two papers by Lu and colleagues(Reference Lu, Anderson and Grady26), the intake of 36 Oz/d of soy milk (~200mg/d IF) for 1 month caused a reduction in mean estradiol levels of 31% at days 57, P=009; 81% at days 1214, P=003; 49% at days 2022, P=002, compared with the baseline. The sooner you take it the more eggs start to mature and the later it focuses on the quality of the most maturing egg, or at least this is what I read. United States California With regards to available clinical trials, Lu and colleagues conducted two interventional studies using 36 Oz of soy milk (about one litre) divided into three daily intakes for a total daily intake of about 200mg of isoflavones(Reference Lu, Anderson and Grady26,Reference Lu, Anderson and Grady29) . Recently, the anti-Mllerian hormone (AMH) concentrations have proved to be a useful tool for predicting female fertility, especially because it is independent of the cycle phase(Reference Dewailly and Laven48). However, in the work of Filiberto and colleagues(Reference Filiberto, Mumford and Pollack37), even if the correlation between isoflavones and the increase in SHBG was highlighted, the dosage of estradiol and free estradiol did not show significant correlations, although the estimate of free estradiol was done through Sodergard's formula(Reference Sdergrd, Bckstrm and Shanbhag61), so a direct dosage would be more reliable. M. L. contributed to drafting and revising the manuscript. The obtained results were evaluated for duplicates and then screened for titles and abstracts information. FSH levels were not significantly changed after genistein intervention. Soy consumption was not related to estradiol levels or endometrial thickness. WHAT IS IT? Total loading time: 0 In addition, other studies investigated the urinary concentrations of isoflavones and metabolites, including equol(Reference Mumford, Sundaram and Schisterman39,Reference Levine, Kim and Purdue-Smithe45) . There is a limited trend in estradiol reduction related to soy consumption; however, in their interventional study, Petrakis and colleagues observed an unusual increase of estradiol levels(Reference Petrakis, Barnes and King25). Similar to the previous observational study, Chavarro et al. Published by Cambridge University Press on behalf of The Nutrition Society. The concomitant treatment with soybean phytoestrogens significantly increased the implantation rate (254% v. 202%; P<005), the pregnancy rate (393% v. 209%; P<005) and the pregnancy-to-delivery rate (303% v. 162%; P<005) compared with placebo. M. A. S. contributed to drafting and revising the manuscript. Last but not least, soy isoflavones can act through an antioxidant mechanism through the stimulation of enzymes responsible for xenobiotics metabolism and oxidative stress reduction in vitro at a range of 5100M(Reference Wei, Wei and Frenkel87). Consequently, the absence of fertility, called infertility, is a disease characterised by the failure to establish a clinical pregnancy and it can depend on various factors including predisposition and behavioural/environmental aspects. After 6 months, estradiol levels of patients in the intervention group were higher compared with basal (P<005), whereas luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were unchanged. Mildly increased levels of SHBG were associated with higher dietary isoflavone intakes (Q4 [16788mg/d] v. Q1 [0003mg/d]) in the adjusted linear mixed model (: 009, 95% CI 002, 016), but no correlation was found for estradiol, progesterone, LH, FSH levels or anovulatory events. The effects obtained from selected studies do not seem to show a clear significance regarding fertility and menstrual cycle length, as discussed in the previous paragraph. Furthermore, there was no evaluation of metabolic utilisation capacity of isoflavones and their absorption by measuring serum and urinary levels. It is plausible that isoflavones bind to this blood carrier and stimulate its hepatic synthesis. The power analysis concerning variation in isoflavone urinary excretion accounted for a sample size of 25 for >90% detection power. This latter aspect suggests a differential capacity for metabolising isoflavones even if these differences were no longer significant when corrected for the intake of isoflavones and estradiol levels were not significantly associated with urinary excretion of isoflavones. Although some works investigate the relationship between consumption of soy formulations in infancy and age at menarche, as well as the onset of puberty or pre-puberty reproductive organ size, these outcomes are not strictly related to fertility in reproductive age(Reference Andres, Moore and Linam69Reference Sinai, Ben-Avraham and Guelmann-Mizrahi71). Isoflavones concentrations did not show significant differences between participants at baseline. Eleven interventional studies, eleven observational studies and one meta-analysis have been selected from the results of queries. Among the six women in the first clinical trial(Reference Lu, Anderson and Grady26), the intervention with soy also led to a significant reduction in dehydroepiandrosterone sulphate (DHEAS) levels (23%, P=003), an intermediary in estradiol synthesis. Furthermore, the nutritional habits of Adventists differ from the Western population ones and they show soy consumption more similar to populations in South-East Asia(Reference Messina53). [1] Conversely, the improvements in ovulation were seen only in two patients from the control group. However, levels of progesterone, estradiol, free estradiol, estrone and SHBG did not show significant differences. Isoflavone genistein inhibited the enzyme tyrosine kinase in human A431 cell membranes at 07g/ml, a very high, non-physiological concentration(Reference Akiyama, Ishida and Nakagawa77) and act as a ligand for peroxisome proliferator-activated receptors (PPARs) in cultured astrocytes at 500nM(Reference Valles, Dolz-Gaiton and Gambini78). Recently, Wesselink and colleagues evaluated the fertility of 7778 healthy American or Canadian women in two cohort studies that followed participants for 12 months or until pregnancy(Reference Wesselink, Hatch and Mikkelsen44). Furthermore, diet and energy intake were not investigated and sampling was not well-timed to menstrual cycle. Introduction. Among the studies discussed to evaluate menstrual cycle length, three interventional studies also evaluated the levels of circulating hormones following soy intake in healthy women(Reference Lu, Anderson and Grady26,Reference Wu, Stanczyk and Hendrich28,Reference Lu, Anderson and Grady29) . However, a clear effect on reproductive system has never been highlighted, especially due to the absence of observational studies designed for this purpose. Even if serum AMH concentrations appear as a useful tool for predicting female fertility, only one study from our selection used them(Reference Haudum, Lindheim and Ascani46). Table 2 summarises main limitations about the studies discussed. However, in multiple regression analysis, this reduction seemed to be significantly associated with the intake of genistein and daidzein or their concentration in urine. Zhang, Yuehui However, after removing data from studies with elevated bias risk, two studies were included in the sensitivity analysis with a consequent loss of statistical significance for LH levels. For this reason, they are classified as phytoestrogensplant-derived compounds with estrogenic activity (1). Adapted from SMART: Servier Medical Art, https://creativecommons.org/licenses/by/4.0/. To our knowledge, this is the first comprehensive review on soy effect on women's fertility. Both isoflavones are found in soy at several mg 100 g 1 ( Bennetau-Pelissero, 2013 ). Furthermore, no characterisation was made on the possible presence of equol-producers among the participants. However, the work had several strengths: the real evaluation of luteal and follicular phase through the dosage of urinary LH:creatinine ratio, the characterisation of sampling according to the cycle; the evaluation of isoflavone content in foods used for the intervention and quantification of urinary isoflavones to check compliance; the use of soy foods and not supplements or extracts to approach a real-life pattern; the characterisation of diet at various steps of clinical trial to avoid confounding mechanisms; the stratification by ethnicity which indirectly showed the effect on equol-producer individuals. The study included the evaluation of patients microbiota composition as the primary endpoint, but androgen levels were also evaluated with AMH as markers of fertility as a secondary endpoint. 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